The objective of this proposed research is to obtain basic knowledge of the role of metabolism, nutrition and genetic factors in the problems of obesity in humans by studying experimental obesity in rats and mice at the cellular and tissue level. The relationship of obesity to abnormal function of the hormones, insulin, glucagon, thyroxine and catecholamines, and to abnormal lipid and carbohydrate metabolism will be investigated as well as the effects of the anorectic drug, fenfluramine, on these. Apparent defects in lipolysis and thermogenesis in obesity will be studied by in vivo and in vitro studies of free fatty acid and epinephrine metabolism during cold exposure in genetically obese hyperglycemic mice with later comparisons to other forms of experimental obesity. The usefulness of fenfluramine in reversing the diabetes associated with obesity in both obese hyperglycemic and obese diabetic mice will also be assessed. Further studies will evaluate the role of dietary sucrose and insulin on the hypertriglyceridemia and hyperinsulinemia present in Zucker fatty rats. The effects of high fat and high carbohydrate diets on obesity will be measured by studying fatty acid and triglyceride biosynthesis in isolated adipocytes and by assaying for lipoprotein lipase activity in tissues of animals fed these diets.